The objective of this career development award is to provide the candidate, Dr. Cielito Reyes-Gibby, the experience and knowledge necessary to apply molecular/genetic epidemiology and advanced statistical methods to the study of cancer-related symptoms. Dr. Reyes-Gibby's career goal is to become an established symptom researcher. This goal builds upon her previous training in epidemiology, statistics, survey research, and nursing. Her transition from that of a recently promoted Assistant Professor to an independent researcher will take place at the Department of Symptom Research at U.T.M.D. Anderson Cancer Center (UTMDACC) in Houston. Dr. Reyes-Gibby has developed a comprehensive education plan that will provide intensive instruction in the areas of molecular/genetic epidemiology, advanced statistics, and immunology. She has chosen three mentors who will supervise her training. Dr. Charles Cleeland will provide mentorship in symptom research; Dr. Margaret Spitz will provide mentorship in molecular and genetic epidemiology; and Dr. Razelle Kurzrock will provide mentorship in cytokine research. She will attend graduate courses at the U.T. School of Public Health and U.T School of Biological Sciences. For her proposed research, Dr. Reyes-Gibby will incorporate genetic data in developing robust quantitative models for the time course of symptoms in relation to lung cancer therapy. Her specific hypothesis is that cytokine gene polymorphism will be a predictor of symptom outcomes. If confirmed, this hypothesis creates a better understanding of the molecular basis of symptom production and a foundation for a new approach to the treatment of severe and persistent symptoms. The studies proposed are designed to build upon an NIH-funded (Charles Cleeland, PhD, Principal Investigator) longitudinal study of symptoms of lung cancer patients (NSCLC, advanced stage) admitted for first line chemotherapy at UT MDACC and an American Cancer Society-funded (Charles Cleeland, PhD, Principal Investigator) longitudinal study of symptom of lung cancer patients (NSCLC stage I-IliA) undergoing curative surgery at the UTMDACC. These funded studies provide the opportunity to assess the relationship between gene polymorphisms and symptoms related to disease stage (late stage for study 1 and early stage disease for study 2) and therapy (chemotherapy and surgical therapy). Since lung cancer patients suffer from severe debilitating symptoms and lung cancer is the leading cause of cancer mortality for men and women in the United States, the findings from this project have immense public health significance.